Phosphodiesterases (“PDEs”) are a family of enzymes involved in regulating intracellular signalling. PDEs act by cleaving the intracellular second messengers cyclic AMP (“cAMP”) and cyclic GMP (“cGMP”). Among the PDEs, PDE IV is the major cAMP metabolizing enzyme found in inflammatory and immune cells. PDE IV inhibitors have been investigated as anti-inflammatory treatments in airway diseases, including the treatment of asthma and chronic obstructive pulmonary disease (COPD).
U.S. patent application Ser. No. 10/821,642 (the '642 application), published as Publication No. 2005/0027129, discloses novel heterocyclic compounds for use as PDE IV inhibitors, the disclosure of which is incorporated by reference in its entirety. In addition, the '642 application discloses a multi-step synthesis of N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide and the corresponding sodium salt. One such compound is N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide sodium salt, represented by the following formula:

International Publication No. WO 2006/040652 also discloses methods for preparing N-(3,5 dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide and its sodium salt, the disclosure of which is incorporated by reference in its entirety.
However, there remains a need in the art to provide methods for the synthesis of N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-methanesulfonamido-dibenzo[b,d]furan-1-carboxamide and pharmaceutically acceptable salts thereof.